A prominent feature of a canine disorder considered to represent an increase of peroxidation in English setters is the accumulation of lipopigments in all tissues including the retina and pigment epithelium. Lipids containing highly unsaturated fatty acids are thought to be damaged through a free radical-peroxide mechanism. We have discovered a specific deficiency of peroxidase in the retina and pigment epithelium that could explain how free-radicals are produced through an increase in hydrogen peroxide. During the first 2 years dogs with this disorder will be treated with antioxidants, enzyme replacement or enhancing enzyme activity. Micro assays will be established for 1) p-phenylenediamine peroxidase, 2) glutathione peroxidase, catalase, and superoxide dismutase, 3) lipoxygenase and desaturases, and 4) hydrogen peroxide lipid peroxides and free radicals. Isoenzymes will be separated on acrylamide gels. Monospecific antibodies to horseradish peroxidase will be used to identify exogenous peroxidase in retina and pigment epithelium. A procedure for isolating purified lipopigments and a complete fatty acid analysis on these tissues will be established. Tissue cultures of pigment epithelium will be grown to study phagocytosis, other physiologic functions, and enzyme distribution. Our ERG facility will be adapted for animal use and optimal conditions for uniform recording work out. In the final three years, treated affected animals will be compared to untreated littermates with respect to 1) life span and clinical condition, 2) visual acuity and ERG response, 3) pathology (light and EM), biochemistry, and enzymology, of the retina, photoreceptors and pigment epithelium. The accomplishment of this large number of complicated experiments is possible within this 5 year time span because of the mutual interest of specialists from collaborating laboratories.